Within- and between-person effects of naltrexone on the subjective response to alcohol and craving: A daily diary investigation

Jack T. Waddell, William R. Corbin, David P. MacKinnon, Robert F. Leeman, Kelly S. DeMartini, Lisa M. Fucito, Henry R. Kranzler, Stephanie S. O’Malley

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Objective: Naltrexone is an effective treatment for heavy drinking among young adults. Laboratory-based studies have shown that naltrexone dampens the subjective response to alcohol and craving. However, few studies have tested naltrexone's dynamic, within-person effects on subjective response and craving among young adults in natural drinking environments. Methods: Using daily diary data from a randomized, placebo-controlled study of naltrexone's efficacy in young adults, we examined the between-person effects of treatment condition (i.e., naltrexone vs. placebo) and medication dosage (i.e., daily, targeted, and daily + targeted) on the subjective response to alcohol and craving on drinking days. Multilevel mediation models predicted subjective response and craving from treatment condition (between-person) and medication dosage (within-person), accounting for drinking levels. All effects were disaggregated within and between persons. Results: At the between-person level, naltrexone directly blunted intense subjective effects (i.e., “impaired”, “drunk”) and indirectly blunted subjective effects through reduced drinking. Naltrexone was not associated with craving. Between-person effects were not significant after alpha correction, but their effect sizes (bs = 0.14 to 0.17) exceeded the smallest effect size of interest. At the within-person level, taking two (vs. 1) pills was associated with heavier drinking, and taking one (vs. 0) pill was associated with lighter drinking, and lighter drinking was associated with a lower subjective response and craving. Treatment condition did not moderate the within-person effects of dosing on outcomes. Conclusions: Our findings suggest that the direct between-person effect of naltrexone was largest on intense subjective responses, blunting feelings of being “drunk” and “impaired”. Future research using momentary (rather than daily) assessments could confirm and extend these findings.

Original languageEnglish (US)
Pages (from-to)477-491
Number of pages15
JournalAlcoholism: Clinical and Experimental Research
Issue number3
StatePublished - Mar 2022


  • craving
  • heavy drinking
  • naltrexone
  • subjective response

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health


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